U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from GEO Profiles

    • Showing Current items.

    OTULIN OTU deubiquitinase with linear linkage specificity [ Homo sapiens (human) ]

    Gene ID: 90268, updated on 3-Nov-2024

    Summary

    Go to the top of the page Help
    Official Symbol
    OTULINprovided by HGNC
    Official Full Name
    OTU deubiquitinase with linear linkage specificityprovided by HGNC
    Primary source
    HGNC:HGNC:25118
    See related
    Ensembl:ENSG00000154124 MIM:615712; AllianceGenome:HGNC:25118
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GUM; AIPDS; IMD107; FAM105B
    Summary
    This gene encodes a member of the peptidase C65 family of ubiquitin isopeptidases. Members of this family remove ubiquitin from proteins. The encoded enzyme specifically recognizes and removes M1(Met1)-linked, or linear, ubiquitin chains from protein substrates. Linear ubiquitin chains are known to regulate the NF-kappa B signaling pathway in the context of immunity and inflammation. Mutations in this gene cause a potentially fatal autoinflammatory syndrome in human patients. [provided by RefSeq, Sep 2016]
    Expression
    Ubiquitous expression in bone marrow (RPKM 5.9), skin (RPKM 4.5) and 25 other tissues See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    See OTULIN in Genome Data Viewer
    Location:
    5p15.2
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (14664718..14716525)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (14604209..14656024)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (14664827..14699959)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene eukaryotic translation elongation factor 1 alpha 1 pseudogene 13 Neighboring gene small nucleolar RNA, C/D box 141B Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:14663902-14664704 Neighboring gene Sharpr-MPRA regulatory region 4048 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22409 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22410 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22411 Neighboring gene OTULIN divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22412 Neighboring gene uncharacterized LOC100130744 Neighboring gene uncharacterized LOC124900944 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22413 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:14727488-14727682 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:14727811-14728770 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:14728771-14729729 Neighboring gene ANKH inorganic pyrophosphate transport regulator Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22414 Neighboring gene RBBP4 pseudogene 1

    Genomic regions, transcripts, and products

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    Go to the top of the pageHelp

    Related articles in PubMed

    1. OTULIN Haploinsufficiency Causes Hyperinflammatory Responses to Infectious and Non-Infectious Triggers. Batlle-Masó L, et al. J Clin Immunol, 2024 Apr 5. PMID 38578307
    2. Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker. Huang Z, et al. Front Biosci (Landmark Ed), 2023 Nov 27. PMID 38062820
    3. Downregulation of otulin induces inflammasome activation in neutrophilic asthma. Quoc QL, et al. J Allergy Clin Immunol, 2024 Sep. PMID 38599290
    4. Post-translational Modification of OTULIN Regulates Ubiquitin Dynamics and Cell Death. Douglas T, et al. Cell Rep, 2019 Dec 10. PMID 31825842
    5. Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin. Spaan AN, et al. Science, 2022 Jun 17. PMID 35587511, Free PMC Article

    See all (81) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Downregulation of otulin induces inflammasome activation in neutrophilic asthma.
      Title: Downregulation of otulin induces inflammasome activation in neutrophilic asthma.
    2. OTULIN Haploinsufficiency Causes Hyperinflammatory Responses to Infectious and Non-Infectious Triggers.
      Title: OTULIN Haploinsufficiency Causes Hyperinflammatory Responses to Infectious and Non-Infectious Triggers.
    3. Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker.
      Title: Integrated Single-Cell and Transcriptome Sequencing Analyses Develop a Ubiquitination-Associated Signature in Gastric Cancer and Identified OTULIN as a Novel Biomarker.
    4. An interaction between OTULIN and SCRIB uncovers roles for linear ubiquitination in planar cell polarity.
      Title: An interaction between OTULIN and SCRIB uncovers roles for linear ubiquitination in planar cell polarity.
    5. Reciprocal interplay between OTULIN-LUBAC determines genotoxic and inflammatory NF-kappaB signal responses.
      Title: Reciprocal interplay between OTULIN-LUBAC determines genotoxic and inflammatory NF-κB signal responses.
    6. Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin.
      Title: Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin.
    7. LUBAC and OTULIN regulate autophagy initiation and maturation by mediating the linear ubiquitination and the stabilization of ATG13.
      Title: LUBAC and OTULIN regulate autophagy initiation and maturation by mediating the linear ubiquitination and the stabilization of ATG13.
    8. OTULIN protects the liver against cell death, inflammation, fibrosis, and cancer.
      Title: OTULIN protects the liver against cell death, inflammation, fibrosis, and cancer.
    9. Post-translational Modification of OTULIN Regulates Ubiquitin Dynamics and Cell Death.
      Title: Post-translational Modification of OTULIN Regulates Ubiquitin Dynamics and Cell Death.
    10. ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/beta-catenin activation to enhance drug resistance in breast cancers.
      Title: ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/β-catenin activation to enhance drug resistance in breast cancers.
    Submit: New GeneRIF Correction See all GeneRIFs (21)

    Phenotypes

    Go to the top of the page Help

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection
    MedGen: C5774192 OMIM: 619986 GeneReviews: Not available
    		not available
    Infantile-onset periodic fever-panniculitis-dermatosis syndrome
    MedGen: C4310614 OMIM: 617099 GeneReviews: Not available
    		Compare labs

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

    Go to the top of the page

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    Markers

    Homology

    Clone Names

    • FLJ34884

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cysteine-type deubiquitinase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables cysteine-type deubiquitinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cysteine-type deubiquitinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cysteine-type deubiquitinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables cysteine-type peptidase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in innate immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in innate immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in innate immune response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of NF-kappaB transcription factor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of inflammatory response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of inflammatory response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in nucleotide-binding oligomerization domain containing 2 signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein linear deubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination TAS
    Traceable Author Statement
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of canonical Wnt signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of tumor necrosis factor-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of tumor necrosis factor-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in sprouting angiogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    part_of LUBAC complex IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

    Go to the top of the page Help
    Preferred Names
    ubiquitin thioesterase otulin
    Names
    OTU domain-containing deubiquitinase with linear linkage specificity
    deubiquitinating enzyme otulin
    family with sequence similarity 105, member B
    ubiquitin thioesterase Gumby
    NP_612357.4
    XP_011512453.1
    XP_011512456.1
    XP_016865504.1
    XP_047273820.1
    XP_054209727.1
    XP_054209728.1
    XP_054209729.1

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_051625.1 RefSeqGene

      Range
      8925..44057
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_138348.6 → NP_612357.4  ubiquitin thioesterase otulin

      See identical proteins and their annotated locations for NP_612357.4

      Status: REVIEWED

      Source sequence(s)
      AC010491, BC007706, BC015392, CK817982, DB238080
      Consensus CDS
      CCDS43302.1
      UniProtKB/Swiss-Prot
      D3DTD3, Q8NAS0, Q96BN8, Q96IA3
      Related
      ENSP00000284274.4, ENST00000284274.5
      Conserved Domains (1) summary
      pfam16218
      Location:81 → 344
      Peptidase_C101; Peptidase family C101

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      14664718..14716525
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011514151.3 → XP_011512453.1  ubiquitin thioesterase otulin isoform X1

      See identical proteins and their annotated locations for XP_011512453.1

      UniProtKB/Swiss-Prot
      D3DTD3, Q8NAS0, Q96BN8, Q96IA3
      Related
      ENSP00000520900.1, ENST00000850613.1
      Conserved Domains (1) summary
      pfam16218
      Location:81 → 344
      Peptidase_C101; Peptidase family C101

    2. XM_011514154.3 → XP_011512456.1  ubiquitin thioesterase otulin isoform X4

      Conserved Domains (1) summary
      pfam16218
      Location:81 → 254
      Peptidase_C101; Peptidase family C101

    3. XM_017010015.2 → XP_016865504.1  ubiquitin thioesterase otulin isoform X3

    4. XM_047417864.1 → XP_047273820.1  ubiquitin thioesterase otulin isoform X2

    RNA

    1. XR_007058658.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      14604209..14656024
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054353752.1 → XP_054209727.1  ubiquitin thioesterase otulin isoform X1

      UniProtKB/Swiss-Prot
      D3DTD3, Q8NAS0, Q96BN8, Q96IA3

    2. XM_054353754.1 → XP_054209729.1  ubiquitin thioesterase otulin isoform X4

    3. XM_054353753.1 → XP_054209728.1  ubiquitin thioesterase otulin isoform X3

    RNA

    1. XR_008487194.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96BN8.3 GenPept UniProtKB/Swiss-Prot:Q96BN8

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous